Evaluation of the effects of ezetimibe on albuminuria and kidney fat in individuals with type 2 diabetes and chronic kidney disease.

AIM: To investigate the effects of ezetimibe on the urine albumin creatinine ratio (UACR) and kidney parenchyma fat content (kidney-PF) in individuals with type 2 diabetes (T2D) and early chronic kidney disease. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled study of ezetimibe 10 mg once daily for 16 weeks in individuals with T2D and a UACR of 30 mg/g or higher was conducted. Kidney-PF was assessed with magnetic resonance spectroscopy. Geometric mean changes from baseline were derived from linear regressions. RESULTS: A total of 49 participants were randomized to ezetimibe (n = 25) or placebo (n = 24). Overall, mean ± standard deviation age was 67 ± 7 years, body mass index was 31 ± 4 kg/m2 and the proportion of men was 84%. The mean estimated glomerular filtration rate was 76 ± 22 mL/min/1.73m2 and median (first-third quartile) UACR was 95 (41-297) mg/g. Median kidney-PF was 1.0% (0.3%-2.1%). Compared with placebo, ezetimibe did not significantly reduce UACR (mean [95% confidence interval] change: -3% [-28%-31%]) or kidney-PF (mean change: -38% [-66%-14%]). In participants with baseline kidney-PF above the median, ezetimibe reduced kidney-PF significantly (mean change: -60% [-84%--3%]) compared with placebo, while the reduction in UACR was not significant (mean change: -28% [-54%-15%]). CONCLUSIONS: Ezetimibe did not reduce the UACR or kidney-PF on top of modern T2D management. However, kidney-PF was reduced with ezetimibe in participants with high baseline kidney-PF.

Age- and sex-specific changes in visceral fat mass throughout the life-span.

OBJECTIVE: Visceral fat mass (VFM) is a risk factor for cardiovascular diseases, type 2 diabetes mellitus, and malignancy; however, normative data are limited. The aim of this study was to provide reference data for VFM from a large, apparently healthy Caucasian adult population. METHODS: Volunteers aged 20 to 93 years from the Copenhagen City Heart Study had a standardized whole-body dual-energy x-ray absorptiometry scan performed using the iDXA (GE Lunar). Total and regional fat mass was measured. VFM was quantified using the CoreScan application. RESULTS: A total of 1277 participants were included (708 women, mean [SD], age: 56 [19] years, height: 1.66 [0.07] m, BMI: 24.64 [4.31] kg/m2 ; and 569 men, age: 57 [18] years, height: 1.80 [0.07] m, BMI: 25.99 [3.86] kg/m2 ). Increased VFM was positively correlated with age in both sexes. Men had significantly higher VFM in mass (g) after normalization to body size (m2 ) and total fat mass (p < 0.001). VFM increased more in women with high values of the android/gynoid ratio. CONCLUSIONS: Normative data of VFM from a large, healthy Danish cohort aged 20 to 93 years are presented. VFM increased with age in both sexes, but men had significantly higher VFM compared with women with the same BMI, body fat percentage, and fat mass index.

Multiparametric magnetic resonance imaging: A robust tool to test pathogenesis and pathophysiology behind nephropathy in humans.

Chronic kidney disease (CKD) is a major population disease. In diabetes as well as hypertension, kidney disease is one of the most serious complications. Recent research has demonstrated that chronic hypoxia is a key actor in the pathogenesis of CKD. In this review, we focus on how functional magnetic resonance imaging (fMRI) techniques can shed light on pathogenetic mechanisms and monitor new treatments aimed at preventing or ameliorating the disease. Multiparametric MRI techniques can measure changes in renal artery flow, tissue perfusion, and oxygenation repetitively over short time periods, enabling high time resolution. Furthermore, renal fibrosis can be quantified noninvasively by MRI diffusion tensor imaging, and techniques are upcoming to measure renal oxygen consumption. These techniques are all radiation and contrast-free. We briefly present data, demonstrating that fMRI techniques can play a major role in future research in CKD, and possibly also in daily clinical practice.

GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading.

Background GLP-1 (glucagon-like peptide-1) receptor agonists exert beneficial long-term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP-1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (-5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP-1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP-1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP-1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268.

Multimodality Imaging in Cranial Giant Cell Arteritis: First Experience with High-Resolution T1-Weighted 3D Black Blood without Contrast Enhancement Magnetic Resonance Imaging.

In order to support or refute the clinical suspicion of cranial giant cell arteritis (GCA), a supplemental imaging modality is often required. High-resolution black blood Magnetic Resonance Imaging (BB MRI) techniques with contrast enhancement can visualize artery wall inflammation in GCA. We compared findings on BB MRI without contrast enhancement with findings on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/low-dose computed tomography (2-[18F]FDG PET/CT) in ten patients suspected of having GCA and in five control subjects who had a 2-[18F]FDG PET/CT performed as a routine control for malignant melanoma. BB MRI was consistent with 2-[18F]FDG PET/CT in 10 out of 10 cases in the group with suspected GCA. In four out of five cases in the control group, the BB MRI was consistent with 2-[18F]FDG PET/CT. In this small population, BB MRI without contrast enhancement shows promising performance in the diagnosis of GCA, and might be an applicable imaging modality in patients.

Development of an Extended-Reality (XR)-Based Intervention to Treat Adolescent Obesity.

Public health policies aimed at obesity reduction are more often directed toward adults than children. This is alarming given that rates of childhood obesity have been steadily increasing, and, if not treated early, adolescents with obesity may develop comorbidities into adulthood. Lifestyle-based interventions are the cornerstone of childhood obesity treatment. Recently, extended-reality (XR)-based interventions have been incorporated into the treatment of obesity, and parents and adolescents perceive virtual reality (VR) interventions as a promising approach to increasing physical activity levels and improving eating habits. VR is a tool that fits perfectly with contemporary adolescent culture, which is radically different from that of just two generations ago. It is plausible that an XR-based intervention for treating adolescents with obesity could have a profound influence on obesity management over the long-term. An understanding of adolescents' preferences, wants, and needs must be considered in the development of new interventions. We suggest that VR interventions can provide a new approach to weight management for children and adolescents and provide recommendations to assess adolescents', caregivers', and primary care providers' needs. These needs could then be used for the development of an XR-based intervention aimed at inducing sustained lifestyle changes in adolescents with obesity.

Kidney oxygenation, perfusion and blood flow in people with and without type 1 diabetes.

Background: We used magnetic resonance imaging (MRI) to study kidney energetics in persons with and without type 1 diabetes (T1D). Methods: In a cross-sectional study, 15 persons with T1D and albuminuria and 15 non-diabetic controls (CONs) underwent multiparametric MRI (3 Tesla Philips Scanner) to quantify renal cortical and medullary oxygenation (R2*, higher values correspond to higher deoxyhaemoglobin concentration), renal perfusion (arterial spin labelling) and renal artery blood flow (phase contrast). Analyses were adjusted for age, sex, systolic blood pressure, plasma haemoglobin, body mass index and estimated glomerular filtration rate (eGFR). Results: Participants with T1D had a higher median (Q1; Q3) urine albumin creatinine ratio (UACR) than CONs [46 (21; 58) versus 4 (3; 6) mg/g; P < .0001] and a lower mean ± SD eGFR (73 ± 32 mL/min/1.73 m2 versus 88 ± 15 mL/min/1.73 m2;  P = .12), although not significantly. Mean medullary R2* was lower in T1D (34 ± 6/s versus 38 ± 5/s; P < .01) corresponding to a higher oxygenation. R2* was not different in the cortex. Cortical perfusion was lower in T1D (163 ± 40 versus 224 ± 49 mL/100 g/min; P < .001). Renal artery blood flow was lower in T1D than in CONs (360 ± 130 versus 430 ± 113 mL/min; P = .05). In T1D, lower cortical oxygenation and renal artery blood flow were both associated with higher UACR and lower eGFR (P < .05). Conclusions: Participants with T1D and albuminuria exhibited higher medullary oxygenation than CONs, despite lower cortical perfusion and renal artery blood flow. This might reflect perturbed kidney energetics leading to a higher setpoint of medullary oxygenation in T1D. Lower cortical oxygenation and renal artery blood flow were associated with higher UACR and lower eGFR in T1D.

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study.

BACKGROUND: Although growth differentiation factor 15 (GDF15) is known to increase with disease and is associated with low physical performance, the role of GDF15 in normal ageing is still not fully understood. Specifically, the influence of circulating GDF15 on impairments in maximal muscle power (a major contributor to functional limitations) and the underlying components has not been investigated. METHODS: Data from 1305 healthy women and men aged 20 to 93 years from The Copenhagen Sarcopenia Study were analysed. Circulating levels of GDF15 and markers of inflammation (tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein) were measured by ELISA (R&D Systems) and multiplex bead-based immunoassays (Bio-Rad). Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to leg muscle mass) muscle power were assessed by the Nottingham power rig [leg extension power (LEP)] and the 30 s sit-to-stand (STS) muscle power test. Total body fat, visceral fat, and leg lean mass were assessed by dual energy X-ray absorptiometry. Leg skeletal muscle index was measured as leg lean mass normalized to body height squared. RESULTS: Systemic levels of GDF15 increased progressively as a function of age in women (1.1 ± 0.4 pg·mL-1 ·year-1 ) and men (3.3 ± 0.6 pg·mL-1 ·year-1 ) (both P < 0.05). Notably, GDF15 increased at a faster rate from the age of 65 years in women (11.5 ± 1.2 pg·mL-1 ·year-1 , P < 0.05) and 70 years in men (19.3 ± 2.3 pg·mL-1 ·year-1 , P < 0.05), resulting in higher GDF15 levels in men compared with women above the age of 65 years (P < 0.05). Independently of age and circulatory markers of inflammation, GDF15 was negatively correlated to relative STS power (P < 0.05) but not LEP, in both women and men. These findings were mainly explained by negative associations of GDF15 with specific STS power in women and men (both P < 0.05). CONCLUSIONS: A J-shaped relationship between age and systemic GDF15 was observed, with men at older age showing steeper increases and elevated GDF15 levels compared with women. Importantly, circulating GDF15 was independently and negatively associated with relative STS power, supporting the potential role of GDF15 as a sensitive biomarker of frailty in older people.

Associations between inflammatory markers, body composition, and physical function: the Copenhagen Sarcopenia Study.

BACKGROUND: Chronic low-grade inflammation has been suggested as one of the key elements in the development of sarcopenia, but in contrast to disease-related loss of muscle mass, the role of chronic low-grade inflammation in age-related (primary) sarcopenia is still not clear. The aim of this study was to investigate low-grade inflammation in relation to age and the potential association between inflammatory biomarkers and body composition, muscle strength and physical performance in a healthy Danish cohort. METHODS: There were 1160 generally healthy men and women (range: 22-93 years) included. Appendicular lean mass (ALM) and visceral fat normalized to height (kg/m2 ) was assessed by dual-energy X-ray absorptiometry (iDXA, GE Lunar). Muscle strength and physical performance were evaluated by handgrip strength (HGS), 30 s sit-to-stand performance, and maximal gait speed (GS). Systemic levels of TNF-α, IL-6, IL-1ß, IL-4, IL-13, and IFN-γ were measured using multiplex bead-based immunoassays (Bio-Rad). hsCRP was assessed using latex particle-enhanced immunoturbidimetric assays (Roche Diagnostics). RESULTS: With age, ALM/h2 , HGS, sit-to-stand performance and GS decreased, whereas visceral fat/h2 increased in both men and women (P < 0.05). Systemic levels of hsCRP, TNF-α, IL-4, and IFN-γ increased with age in men and women (P < 0.05), while IL-1ß increased in women only (P < 0.01). Higher levels of hsCRP were associated with lower ALM/h2 in elderly (≥65 years) men and women (P < 0.001). Higher levels of hsCRP were associated with lower handgrip strength in elderly women (P < 0.05) whereas higher levels of hsCRP was not associated with lower HGS in elderly men (P = 0.056). Higher levels of hsCRP were associated with lower GS (P < 0.05), whereas IFN-γ was positively associated with GS in elderly women (P < 0.05), but not elderly men. Visceral fat index was positively associated with hsCRP in elderly men and women (P < 0.001). Compared with elderly with normal HGS, elderly men and women with low HGS displayed higher levels of TNF-α and hsCRP (P < 0.05). CONCLUSIONS: With age, systemic levels of hsCRP, TNF-α, IL-4, and IFN-γ increased, with hsCRP and TNF-α being especially elevated in more physically frail elderly supporting the association between low-grade systemic inflammation and poor physical function. In contrast, only high levels of hsCRP were weakly associated with low muscle mass and positively associated with visceral fat and low physical function, suggesting that chronic low-grade inflammation is not the main driver of age-related loss of muscle mass as previously suggested.

Acute effects of dapagliflozin on renal oxygenation and perfusion in type 1 diabetes with albuminuria: A randomised, double-blind, placebo-controlled crossover trial.

BACKGROUND: Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria. METHODS: A randomised, double-blind, placebo-controlled, crossover trial with a single 50 mg dose of the SGLT2 inhibitor dapagliflozin and placebo in random order, separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal R2* (a low value corresponds to a high tissue oxygenation), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline, three- and six hours from tablet ingestion. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation, peripheral blood mononuclear cell mitochondrial oxygen consumption rate, and biomarkers of inflammation were evaluated at baseline and 12 h from medication. The study is registered in the EU Clinical Trials Register (EudraCT 2019-004,557-92), on ClinicalTrials.gov (NCT04193566), and is completed. FINDINGS: Between February 3, 2020 and October 23, 2020, 31 individuals were screened, and 19 eligible individuals were randomised. Three dropped out before receiving any of the interventions and one dropped out after receiving only placebo. We included 15 individuals (33% female) in the per-protocol analysis with a mean age of 58 (SD 14) years, median urinary albumin creatinine ratio of 46 [IQR 21-58] mg/g and an eGFR of 73 (32) ml/min/1·73m2. The mean changes in renal cortical R2* from baseline to six hours were for dapagliflozin -1·1 (SD 0·7) s-1 and for placebo +1·3 (0·7) s-1, resulting in a difference between interventions of -2·3 s-1 [95% CI -4·0 to -0·6]; p = 0·012. No between-intervention differences were found in any other MRI outcomes, physiological parameters or exploratory outcomes. There were no adverse events. INTERPRETATION: A single dose of 50 mg dapagliflozin acutely improved renal cortical R2* without changing renal perfusion or blood flow. This suggests improved renal cortical oxygenation due to a reduced tubular transport workload in the proximal tubules. Such improved oxygenation may in part explain the long-term beneficial renal effects seen with SGLT2 inhibitors, but it remains to be determined whether the observed effects can be achieved with lower doses, with chronic treatment and if they occur in type 2 diabetes as well.

Assessment of functional sit-to-stand muscle power: Cross-sectional trajectories across the lifespan.

BACKGROUND: The 30-s sit-to-stand (STS) muscle power test is a valid test to assess muscle power in older people; however, whether it may be used to assess trajectories of lower-limb muscle power through the adult lifespan is not known. This study evaluated the pattern and time course of variations in relative, allometric and specific STS muscle power throughout the lifespan. METHODS: Subjects participating in the Copenhagen Sarcopenia Study (729 women and 576 men; aged 20 to 93 years) were included. Lower-limb muscle power was assessed with the 30-s version of the STS muscle power test. Allometric, relative and specific STS power were calculated as absolute STS power normalized to height squared, body mass and leg lean mass as assessed by DXA, respectively. RESULTS: Relative STS muscle power tended to increase in women (0.08 ±â€¯0.05 W·kg-1·yr-1; p = 0.082) and increased in men (0.14 ±â€¯0.07 W·kg-1·yr-1; p = 0.046) between 20 and 30 years, followed by a slow decline (-0.05 ±â€¯0.05 W·kg-1·yr-1 and -0.06 ±â€¯0.08 W·kg-1·yr-1, respectively; both p > 0.05) between 30 and 50 years. Then, relative STS power declined at an accelerated rate up to oldest age in men (-0.09 ±â€¯0.02 W·kg-1·yr-1) and in women until the age of 75 (-0.09 ±â€¯0.01 W·kg-1·yr-1) (both p < 0.001). A lower rate of decline was observed in women aged 75 and older (-0.04 ±â€¯0.02 W·kg-1·yr-1; p = 0.039). Similar age-related patterns were noted for allometric and specific STS power. CONCLUSIONS: The STS muscle power test appears to provide a feasible and inexpensive tool to monitor cross-sectional trajectories of muscle power throughout the lifespan.

Exercise-induced fluid shifts are distinct to exercise mode and intensity: a comparison of blood flow-restricted and free-flow resistance exercise.

MRI can provide fundamental tools in decoding physiological stressors stimulated by training paradigms. Acute physiological changes induced by three diverse exercise protocols known to elicit similar levels of muscle hypertrophy were evaluated using muscle functional magnetic resonance imaging (mfMRI). The study was a cross-over study with participants (n = 10) performing three acute unilateral knee extensor exercise protocols to failure and a work matched control exercise protocol. Participants were scanned after each exercise protocol; 70% 1 repetition maximum (RM) (FF70); 20% 1RM (FF20); 20% 1RM with blood flow restriction (BFR20); free-flow (FF) control work matched to BFR20 (FF20WM). Post exercise mfMRI scans were used to obtain interleaved measures of muscle R2 (indicator of edema), R2' (indicator of deoxyhemoglobin), muscle cross sectional area (CSA) blood flow, and diffusion. Both BFR20 and FF20 exercise resulted in a larger acute decrease in R2, decrease in R2', and expansion of the extracellular compartment with slower rates of recovery. BFR20 caused greater acute increases in muscle CSA than FF20WM and FF70. Only BFR20 caused acute increases in intracellular volume. Postexercise muscle blood flow was higher after FF70 and FF20 exercise than BFR20. Acute changes in mean diffusivity were similar across all exercise protocols. This study was able to differentiate the acute physiological responses between anabolic exercise protocols. Low-load exercise protocols, known to have relatively higher energy contributions from glycolysis at task failure, elicited a higher mfMRI response. Noninvasive mfMRI represents a promising tool for decoding mechanisms of anabolic adaptation in muscle.NEW & NOTEWORTHY Using muscle functional MRI (mfMRI), this study was able to differentiate the acute physiological responses following three established hypertrophic resistance exercise strategies. Low-load exercise protocols performed to failure, with or without blood flow restriction, resulted in larger changes in R2 (i.e. greater T2-shifts) with a slow rate of return to baseline indicative of myocellular fluid shifts. These data were cross evaluated with interleaved measures of macrovascular blood flow, water diffusion, muscle cross sectional area (i.e. acute macroscopic muscle swelling), and intracellular water fraction measured using MRI.

Obesity does not modulate men's eating behavior after a high intensity interval exercise session: an exercise trial.

BACKGROUND: We investigated the impact of obesity on responses to high intensity interval exercise (HIIE) on hunger and energy intake (EI) in young men. METHODS: Ten men with obesity (OB) (Body Mass Index [BMI]: 34.6±4.4 kg/m2) and 10 with normal weight (CG) (BMI: 23.1±3.9 kg/m2) participated in a HIIE session. The session consisted of 6 rounds performed at 100% of maximum aerobic velocity (MAV) for 30 seconds, followed by 30 seconds of active recovery at 50% MAV and concluded with 4 minutes of passive recovery. This was repeated three times. EI was estimated at baseline and 24 h-post-HIIE. Hunger was measured at baseline, 2 h- and 24 h-post HIIE. RESULTS: Carbohydrate (CHO) intake increased in both groups (P<0.01). Hunger feelings (19.5 [0-50] mm at baseline to 50 [9-73] mm post-2 h and 60 [8-92] mm in post-24 h [group: P=0.71, time: P<0.01, group × time: P=0.06]) and a desire to eat (34 [1-89] ±36.0 mm at baseline to 63 [11-86] mm post-2 h and 51 [7-84] mm post-24 h [group: P=0.65, time: P<0.01, group × time: P=0.29]) increased in both groups. CONCLUSIONS: Weight status does not modulate hunger and EI post-HIIE. However, the compensatory increase in CHO intake and hunger feelings is particularly noteworthy for health professionals.

Relation between leg extension power and 30-s sit-to-stand muscle power in older adults: validation and translation to functional performance.

This study aimed to assess the validity and functional relevance of a standardized procedure to assess lower limb muscle power by means of the 30-s sit-to-stand (STS) test when compared to leg extension power (LEP), traditional STS performance and handgrip strength. A total of 628 community-dwelling older subjects (60-93 years) from the Copenhagen Sarcopenia Study were included. Physical performance was assessed by the 30-s STS and 10-m maximal gait speed tests. Handgrip strength and LEP were recorded by a hand-held dynamometer and the Nottingham power rig, respectively. STS muscle power was calculated using the subjects' body mass and height, chair height and the number of repetitions completed in the 30-s STS test. We found a small albeit significant difference between LEP and unilateral STS power in older men (245.5 ± 88.8 vs. 223.4 ± 81.4 W; ES = 0.26; p < 0.05), but not in older women (135.9 ± 51.9 vs. 138.5 ± 49.6 W; ES = 0.05; p > 0.05). Notably, a large positive correlation was observed between both measures (r = 0.75; p < 0.001). Relative STS power was more strongly related with maximal gait speed than handgrip strength, repetition-based STS performance and relative LEP after adjusting for age (r = 0.53 vs 0.35-0.45; p < 0.05). In conclusion, STS power obtained from the 30-s STS test appeared to provide a valid measure of bilateral lower limb power and was more strongly related with physical performance than maximal handgrip strength, repetition-based STS performance and LEP.

Physiological responses of human skeletal muscle to acute blood flow restricted exercise assessed by multimodal MRI.

Important physiological quantities for investigating muscle hypertrophy include blood oxygenation, cell swelling, and changes in blood flow. The purpose of this study was to compare the acute changes of these parameters in human skeletal muscle induced by low-load (20% 1-RM) blood flow-restricted (BFR-20) knee extensor exercise compared with free-flow work-matched (FF-20WM) and free-flow 50% 1-RM (FF-50) knee extensor exercise using multimodal magnetic resonance imaging (MRI). Subjects (n = 11) completed acute exercise sessions for each exercise mode in an MRI scanner, where interleaved measures of muscle R2 (indicator of edema), [Formula: see text] (indicator of deoxyhemoglobin), macrovascular blood flow, and diffusion were performed before, between sets, and after the final set for each exercise protocol. BFR-20 exercise resulted in larger acute decreases in R2 and greater increases in cross-sectional area than FF-20WM and FF-50 (P < 0.01). Blood oxygenation decreased between sets during BFR-20, as indicated by a 13.6% increase in [Formula: see text] values (P < 0.01)), whereas they remained unchanged for FF-20WM and decreased during FF-50 exercise. Quadriceps blood flow between sets was highest for the heavier load (FF-50), averaging 305 mL/min, and lowest for BFR-20 at 123 ± 73 mL/min until post-exercise cuff release, where blood flow rates in BFR-20 exceeded both FF protocols (P < 0.01). Acute changes in diffusion rates were similar for all exercise protocols. This study was able to differentiate the acute exercise response of selected physiological factors associated with skeletal muscle hypertrophy. Marked differences in these parameters were found to exist between BFR and FF exercise conditions, which contribute to explain the anabolic potential of low-load blood flow restricted muscle exercise.NEW & NOTEWORTHY Acute changes in blood flow, diffusion, blood oxygenation, cross-sectional area, and the "T2 shift" are evaluated in human skeletal muscle in response to blood flow-restricted (BFR) and conventional free-flow knee extensor exercise performed in an MRI scanner. The acute physiological response to exercise was dependent on the magnitude of load and the application of BFR. Physiological variables changed markedly and established a steady state rapidly after the first of four exercise sets.

Age- and Sex-Specific Changes in Lower-Limb Muscle Power Throughout the Lifespan.

BACKGROUND: Our main goal was to evaluate the pattern and time course of changes in relative muscle power and its constituting components throughout the life span. METHODS: A total of 1,305 subjects (729 women and 576 men; aged 20-93 years) participating in the Copenhagen Sarcopenia Study took part. Body mass index (BMI), leg lean mass assessed by dual-energy X-ray absorptiometry (DXA), and leg extension muscle power (LEP) assessed by the Nottingham power rig were recorded. Relative muscle power (normalized to body mass) and specific muscle power (normalized to leg lean mass) were calculated. Segmented regression analyses were used to identify the onset and pattern of age-related changes in the recorded variables. RESULTS: Relative muscle power began to decline above the age of 40 in both women and men, with women showing an attenuation of the decline above 75 years. Relative muscle power decreased with age due to (i) the loss of absolute LEP after the fourth decade of life and (ii) the increase in BMI up to the age of 75 years in women and 65 years in men. The decline in absolute LEP was caused by a decline in specific LEP up to the age of 75 in women and 65 in men, above which the loss in relative leg lean mass also contributed. CONCLUSIONS: Relative power decreased (i) above 40 years by the loss in absolute power (specific power only) and the increase in body mass, and (ii) above ~70 years by the loss in absolute power (both specific power and leg lean mass).

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation.

Episodic and Chronic Cluster Headache: Differences in Family History, Traumatic Head Injury, and Chronorisk.

OBJECTIVE AND BACKGROUND: The diagnostic criteria of episodic and chronic cluster headache (cCH) were recently modified, yet pathophysiological differences between the two are still unclear. The aim of this cross-sectional study is to identify and characterize other differences between episodic and cCH. METHODS: Data from a retrospective, questionnaire- and interview-based study were analyzed with a focus on associated factors including traumatic head injury (THI), familial history, and change of phenotype. Attack patterns were analyzed using Gaussian and spectral modeling. RESULTS: 400 patients and 200 controls participated. A positive family history was more prevalent in chronic than episodic cluster headache (eCH) (34/146 (23%) vs 33/253 (13%), respectively, P = .008). A history of THI was more common in patients than controls (173/400 (43%) vs 51/200 (26%), respectively, P < .0001) and in chronic compared to eCH (77/146 (53%) vs 96/253 (37%), respectively, P = .004). Patients with a positive family history had a unique diurnal attack pattern with twice the risk of nocturnal attacks as patients who did not report family history. Patients reporting phenotype change had a chronobiological fingerprint similar to the phenotype they had experienced a transition into. A higher attack frequency in chronic patients was the only difference in symptom manifestation across all analyzed subgroups of patients. CONCLUSIONS: cCH is associated with a positive family history and THI. In familial CH, a peak in nocturnal chronorisk may implicate genes involved in diurnal-, sleep- and homeostatic regulation. The stereotypical nature of the CH attacks themselves is confirmed and differences between subgroups should be sought in other characteristics.

A Nordic survey of CT doses in hybrid PET/CT and SPECT/CT examinations.

BACKGROUND: Computed tomography (CT) scans are routinely performed in positron emission tomography (PET) and single photon emission computed tomography (SPECT) examinations globally, yet few surveys have been conducted to gather national diagnostic reference level (NDRL) data for CT radiation doses in positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT). In this first Nordic-wide study of CT doses in hybrid imaging, Nordic NDRL CT doses are suggested for PET/CT and SPECT/CT examinations specific to the clinical purpose of CT, and the scope for optimisation is evaluated. Data on hybrid imaging CT exposures and clinical purpose of CT were gathered for 5 PET/CT and 8 SPECT/CT examinations via designed booklet. For each included dataset for a given facility and scanner type, the computed tomography dose index by volume (CTDIvol) and dose length product (DLP) was interpolated for a 75-kg person (referred to as CTDIvol,75kg and DLP75kg). Suggested NDRL (75th percentile) and achievable doses (50th percentile) were determined for CTDIvol,75kg and DLP75kg according to clinical purpose of CT. Differences in maximum and minimum doses (derived for a 75-kg patient) between facilities were also calculated for each examination and clinical purpose. RESULTS: Data were processed from 83 scanners from 43 facilities. Data were sufficient to suggest Nordic NDRL CT doses for the following: PET/CT oncology (localisation/characterisation, 15 systems); infection/inflammation (localisation/characterisation, 13 systems); brain (attenuation correction (AC) only, 11 systems); cardiac PET/CT and SPECT/CT (AC only, 30 systems); SPECT/CT lung (localisation/characterisation, 12 systems); bone (localisation/characterisation, 30 systems); and parathyroid (localisation/characterisation, 13 systems). Great variations in dose were seen for all aforementioned examinations. Greatest differences in DLP75kg for each examination, specific to clinical purpose, were as follows: SPECT/CT lung AC only (27.4); PET/CT and SPECT/CT cardiac AC only (19.6); infection/inflammation AC only (18.1); PET/CT brain localisation/characterisation (16.8); SPECT/CT bone localisation/characterisation (10.0); PET/CT oncology AC only (9.0); and SPECT/CT parathyroid localisation/characterisation (7.8). CONCLUSIONS: Suggested Nordic NDRL CT doses are presented according to clinical purpose of CT for PET/CT oncology, infection/inflammation, brain, PET/CT and SPECT/CT cardiac, and SPECT/CT lung, bone, and parathyroid. The large variation in doses suggests great scope for optimisation in all 8 examinations.